In Kyung Sung

The role of cytokines in seizures: interleukin (IL)-1β, IL-1Ra, IL-8, and IL-10

Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-1β and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.

The Aristotle score predicts mortality after surgery of patent ductus arteriosus in preterm infants.

BACKGROUND Outcomes after surgical ligation of patent ductus arteriosus (PDA) in preterm infants are often complicated by prematurity associated comorbidities. The Aristotle comprehensive complexity score (ACCS) has been proposed as a useful tool for complexity adjustment in the analysis of outcome after congenital heart surgery. The aims of this study were to define preoperative risk factors for mortality and to demonstrate the usefulness of ACCS to predict mortality after surgical ligation of PDA in the preterm. METHODS Included were 49 preterm babies (≤35 weeks of gestation) who had surgical ligation of PDA between May 2009 and July 2012. Median gestational age was 27.6 weeks (range, 23 to 35 weeks) and median birth weight was 1,040 g (range, 520 to 2,280 g). Median age at operation was 15 days (range, 4 to 44 days) and median weight was 1,120 g (range, 400 to 2,880 g). Initial oral ibuprofen was ineffective in 24 patients and contraindicated in 25. All surgical ligations were done at bedside in the neonatal intensive care unit. Preoperative clinical and laboratory profiles were reviewed and ACCS was derived. RESULTS Eight of 49 patients (16.3%) died at a median of 14 days (range, 2 to 73 days) after PDA ligation. Patients who had contraindications for oral ibuprofen (odds ratio [OR] 8.94; p=0.049), coagulopathy (OR 12.13; p=0.025), renal dysfunction (OR 28.88; p=0.003), intraventricular hemorrhage greater than grade II or seizure (OR 34.00; p=0.002), and ACCS points (OR 29.594; p<0.05) were significantly associated with an increased risk for mortality. Among the risk factors, ACCS showed the largest area under curve (0.991) by receiver-operating characteristic curve analysis. Optimal cutoff value of ACCS for mortality were 15 or greater, with sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 97.6%. CONCLUSIONS The ACCS, especially for procedure-independent complexity factors, is a useful tool to predict mortality after ligation of PDA in preterm infants.

Impact of patient selection on outcomes of PDA in very low birth weight infants

AIM The aim of this study was to observe whether our patient selection maximized the benefits of PDA ligation by comparing the outcomes in a surgically ligated group of PDA to a medically closed group. STUDY DESIGN If a hemodynamically significant ductus arteriosus (HSDA) was found to meet both clinical and echocardiographic criteria (stage≥3), as proposed by NcNamara and Hellman, medical treatment was initiated with oral ibuprofen (maximum 2 courses). If the PDA of these patients failed to close medically, timed surgical closure was performed. RESULT Medical treatment was effective in 75 (72%) cases, and 29 (28%) patients required surgical ligation. The mean gestational age and birth weight were each significantly lower and the initial PDA shunt size was significantly larger in the surgically treated group. Additionally, the mean durations of mechanical ventilation, oxygen dependence and hospital admission were significantly longer in the surgically ligated group. However, our logistic regression analysis demonstrated no statistically significant difference in the outcomes of hospitalization (CLD, NEC, ARF, sepsis, IVH, ROP, PVL and death) between the two groups. CONCLUSION Comprehensive HSDA patient selection may maximize the benefits of timed PDA ligation without adverse outcomes in very low birth weight infants.

The hospital outcomes compared between the early and late hypothermia-treated groups in neonates

Abstract Background and objective: The incidence of hypoxic ischemic encephalopathy (HIE) in developed countries is estimated to be 1.5 per 1000 live births. The primary aim of this study was to analyze whether earlier hypothermia (≤1 h) improves hospital outcomes in survivors who underwent therapeutic hypothermia (TH) when compared with late TH (>1 h). Method: Forty-nine (70%) newborns received TH for 72 h, within 6 h of birth; the remaining 21 received standard care. We divided the TH-treated newborns into early and late groups; early cooling was considered when TH was started ≤1 h after birth; late cooling was considered when started >1 h. Results: The early TH group consisted of 20 of 49 (41%) infants; the late TH group consisted of 29 (59%) infants. Apgar score at 1 min and the initial calcium level was significantly lower in the early (≤1 h) TH infants; there were significantly more inborns in the early TH group (p = 0.008). Infants in the late TH group manifested more clinical seizures followed by more abnormal EEG findings, longer ventilator care and longer hospitalization (p = 0.001). TH-related complications and mortality were not significantly different between the two groups. Conclusions: Early TH (≤1 h) had lower Apgar score at 1 min and initial calcium level, but had decreased incidence of clinico-electrical seizures among HIE infants. Also, ventilator support and hospitalization period were longer in the late TH group.

The Relationship between the Timing of Gestational Diabetes Screening and HbA1c Level and Neonatal Outcome

BACKGROUND The aim of this study was to observe clinical outcomes of the mother and her infant who were possibly exposed to high blood glucose at least 2-3 months in the early and midterm pregnancy by checking gestational weeks (GW) and the first HbA1c level at initial diagnosis of gestational diabetes (GDM). METHODS A total of 107 GDM patients and their newborns were subject of this study. GDM patients were newly diagnosed at the Holy Family Hospital of Catholic University from January 2003 until December 2007 and continuously managed in the diabetes center. Patients medical records were retrospectively reviewed to evaluate GW and HbA1c level at the time of diagnosis, and clinical outcomes of mother and newborn baby. RESULTS The proportion of subjects who had been diagnosed of having GDM according to GW was 7.5%, in less than 24th week of pregnancy; 55.1% in the 24-28th week; 28.0% in the 29-32nd week; and 9.4% 33rd week or more. There were 39 out of 107 subjects (36.4%) with HbA1c levels >or=6.5% and 26 out of 39 subjects (24.3%) with HbA1c levels >or=7.0%. In clinical outcomes of newborn by HbA1c levels, the frequency of delivery of large for gestational age (LGA) infant was higher in mothers diagnosed with GDM after 29th week of pregnancy or with HbA1c levels 7.0% or more (P<0.001). CONCLUSIONS If the screening test for gestational DM was delayed, HbA1c level and the risk for LGA seemed to be higher, so it may be necessary to screen GDM no later than 24th week of pregnancy.

Identification of small marker chromosomes using microarray comparative genomic hybridization and multicolor fluorescent in situ hybridization

BackgroundMarker chromosomes are small supernumerary chromosomes that cannot be unambiguously identified by chromosome banding techniques alone. However, the precise characterization of marker chromosomes is important for prenatal diagnosis and proper genetic counseling. In this study, we evaluated the chromosomal origin of marker chromosomes using a combination of banding cytogenetics and molecular cytogenetic techniques including diverse fluorescence in situ hybridization (FISH) assays and array comparative genomic hybridization (array CGH).ResultsIn a series of 2871 patients for whom cytogenetic analysis was requested, 14 cases with small supernumerary marker chromosomes (sSMCs) were identified. Nine sSMCs were mosaic, and five nonmosaic. Of the nine cases with known parental origins, four were identified as de novo, and four and one were maternally and paternally inherited, respectively. Six sSMCs were identified by FISH using centromeric probes; three sSMCs were derived from chromosome 15, including two heterochromatic sSMC(15)s and a large sSMC(15) spanning 15q11.1q13.1, and three sSMCs originated from chromosome 14 or 22. Array CGH revealed two cases with derivatives of chromosome 2 and whole chromosome painting multicolor-FISH (M-FISH) identified three cases with derivatives of chromosome 6, 16, and 19, respectively. One maker chromosome in Turner syndrome was characterized as sSMC(X) by preferential application of a centromeric probe for X-chromosome. In addition, one sSMC composed of genomic materials from chromosomes 12 and 18 was identified in parallel with parental karyotype analysis that revealed the reciprocal balanced translocation.ConclusionsThis report is the largest study on sSMCs in Korea and expands the spectrum of sSMCs that are molecularly characterized.

Impacts of therapeutic hypothermia on cardiovascular hemodynamics in newborns with hypoxic-ischemic encephalopathy: a case control study using echocardiography

Abstract Purpose: The effects of therapeutic hypothermia (TH) on hemodynamics in newborns with hypoxic-ischemic encephalopathy (HIE) were evaluated. Materials and methods: Thirty-two neonates (gestational age, 39.4 ± 1.3 weeks) who had TH for HIE and echocardiographic hemodynamic assessments during TH and post-TH period were studied. Gestational-age-matched 34 healthy neonates were enrolled for comparison. Results: During TH, patients had significantly decreased left ventricular cardiac output (LVCO), descending aorta blood flow (DABF), and DABF/LVCO ratio, and increased resistive index of DA compared to controls. Upper body blood flow (UBBF) remained unchanged but UBBF/LVCO ratio significantly increased during TH. Urine output decreased significantly during TH and increased after rewarming, and showed significant positive correlation with DABF/LVCO ratio. Sixteen patients (50%) showed hypoxic-ischemic (HI) lesions on brain magnetic resonance imaging (MRI) and had significantly increased UBBF/LVCO ratio during TH compared to patients without HI lesions. Patients with UBBF/LVCO ratio >55% had significantly higher risk of having HI lesions on brain MRI (odds ratio 13.0; 95% CI, 2.4–70.2). Conclusions: Decrease in cardiac output and descending aorta blood flow, and preferential cerebral redistribution of cardiac output along with an increase in systemic peripheral vascular resistance may affect systemic organ perfusion and cerebral metabolism.

Echocardiographic assessment of patent ductus arteriosus in very low birthweight infants over time: prospective observational study

Abstract Background: We aimed to determine the echocardiographic parameters that can predict the presence of patent ductus arteriosus (PDA) and haemodynamically significant ductus arteriosus (HSDA) at different time points. Methods: Echocardiogram was performed on postnatal days 3 and 7(D3-Echo and D7-Echo, respectively) in 71 very low birthweight infants with a median gestational age of 28.0 weeks. We first assessed the correlation between D3-Echo findings among infants with ductal patency and persistent ductal patency on D7-Echo. We subsequently assessed the correlation between D7-Echo findings and ultimate need for PDA treatment. Results: Forty-nine (69.0%) infants had ductal patency on D3-Echo, and 32(65.3%) of these had persistent PDA on D7-Echo. Twenty of the latter (62.5%) underwent PDA treatment at a median chronological age of 19 days. PDA treatment was significantly correlated with DA size and DA peak-systolic-to-end-diastolic velocity(S/D) ratio on D3- and D7-Echo. Receiver operating characteristic curve analysis revealed that DA size ≥2.040 mm and S/D ratio ≥2.016 had fair sensitivity, specificity, and predictive values for PDA treatment. Conclusion: The significance of different echocardiographic parameters associated with future ductal patency or HSDA depends on the time of assessment. DA size and S/D ratio on day 7 are two reliable indicators of the need for future PDA treatment.

Quantitative detection of target cells using unghosted cells (UGCs) of DxH 800 (Beckman Coulter).

Abstract Background: In the Retic channel of DxH 800 (Beckman Coulter), the red blood cells (RBCs) resistant to hemoglobin clearing are counted as unghosted cells (UGCs). The aim of this study was to evaluate that the UGC is a surrogate marker for both the detection and counting of target cells. Methods: In total, 1181 samples including 22 from iron deficiency anemia (IDA) patients, 95 from jaundice, 2 from sickle cell anemia, 3 from thalassemia, 1 cord blood, and 269 from normal controls were analyzed. Slides were prepared from all samples except normal controls and target cells were counted for correlation analysis of target cell counts to UGCs. Results: The normal control samples showed 0.01% (0%–0.01%) UGCs, and the reference range was set at ≤0.02%. The IDA samples showed 0.015% (0.01%–0.03%) UGC count and 0.05% (0%–0.2%) target cell count. The jaundice samples showed 0.98% (0.1%–5.36%) UGC count, and 1.4% (0.1%–7.0%) target cell count. The two sickle cell anemia samples showed 0.41% and 3.74% UGC counts and 0.4% and 11.5% target cell counts. A cord blood sample showed 0.01% UGCs and 0% target cells. The three thalassemia samples showed 0.01%, 1.99%, and 7.82% UGC counts and 0%, 1.4%, and 15.5% target cell counts. The samples showing poikilocytosis other than target cells showed normal UGC count (≤0.02%). The positive predictive value of UGCs was 58.2% (124/213) and the negative predictive value was 96.8% (674/696). The UGC counts were well correlated to the manual target cell counts (r=0.944, p=0.000). Conclusions: This study demonstrates for the first time in the literature that a hematological parameter obtained automatically every time a reticulocyte counting is performed can be used to both screen for the presence of target cells and reliably quantify them.

Impact of histologic chorioamnionitis on pulmonary hypertension and respiratory outcomes in preterm infants

We aimed to evaluate the association between the presence of histologic chorioamnionitis (HC) and development of pulmonary hypertension (PH) during neonatal intensive care unit (NICU) stay. Data of preterm infants born at 32 weeks of gestation or less were reviewed. The development of PH and other respiratory outcomes were compared according to the presence of HC. Potential risk factors associated with the development of PH during NICU stay were used for multivariable logistic regression analysis. A total of 188 infants were enrolled: 72 in the HC group and 116 in the no HC group. The HC group infants were born at a significantly shorter gestational age and lower birthweight, with a greater proportion presenting preterm premature rupture of membrane (pPROM) > 18 h before delivery. More infants in the HC group developed pneumothorax (P = 0.008), and moderate and severe bronchopulmonary dysplasia (BPD; P = 0.001 and P = 0.006, respectively). PH in the HC group was significantly more frequent compared to the no HC group (25.0% versus 8.6%, P = 0.002). Based on a multivariable logistic regression analysis, birthweight (P = 0.009, odds ratio [OR] = 0.997, 95% confidence interval [CI] = 0.995–0.999), the presence of HC (P = 0.047, OR = 2.799, 95% CI = 1.014–7.731), and duration of invasive mechanical ventilation (MV) > 14 days (P = 0.015, OR = 8.036, 95% CI = 1.051–43.030) were significant factors. The presence of HC and prolonged invasive MV in infants with lower birthweight possibly synergistically act against preterm pulmonary outcomes and leads to the development of PH. Verification of this result and further investigation to establish effective strategies to prevent or ameliorate these adverse outcomes are needed.